tbuckley/cabot-search huggingface dataset:
Impact of interstitial lung abnormalities on postoperative pulmonary complications and survival of lung cancer
Authors: Yunjoo Im, Man Pyo Chung, Kyung Soo Lee, Joungho Han, Myung Jin Chung, Hong Kwan Kim, Jong Ho Cho, Yong Soo Choi, Sujin Park, Ho Joong Kim, O Jung Kwon, Boram Park, Hongseok Yoo
Journal: Thorax (2022)

Background Interstitial lung abnormalities (ILAs) are associated with the risk of lung cancer and its mortality. However, the impact of ILA on treatment-related complications and survival in patients who underwent curative surgery is still unknown. Research question This study aimed to evaluate the significance of the presence of computed tomography-diagnosed ILA and histopathologically matched interstitial abnormalities on postoperative pulmonary complications (PPCs) and the long-term survival of patients who underwent surgical treatment for lung cancer. Study design and methods A matched case–control study was designed to compare PPCs and mortality among 50 patients with ILA, 50 patients with idiopathic pulmonary fibrosis (IPF) and 200 controls. Cases and controls were matched by sex, age, smoking history, tumour location, the extent of surgery, tumour histology and pathological TNM stage. Results Compared with the control group, the OR of the prevalence of PPCs increased to 9.56 (95% CI 2.85 to 32.1, p&lt;0.001) in the ILA group and 56.50 (95% CI 17.92 to 178.1, p&lt;0.001) in the IPF group. The 5-year overall survival (OS) rates of the control, ILA and IPF groups were 76% (95% CI 71% to 83%), 52% (95% CI 37% to 74%) and 32% (95% CI 19% to 53%), respectively (log-rank p&lt;0.001). Patients with ILA had better 5-year OS than those with IPF (log-rank p=0.046) but had worse 5-year OS than those in the control group (log-rank p=0.002). Conclusions The presence of radiological and pathological features of ILA in patients with lung cancer undergoing curative surgery was associated with frequent complications and decreased survival.
PATH-11. Detection of genetic and epigenetic alterations in Liquid Biopsies from pediatric brain tumor patients
Authors: Tom T Fischer, Kendra K Maaß, Pitithat Puranachot, Agnes M E Finster, Markus Mieskolainen, Paulina S Schad, Martin Sill, Fabian Rosing, Tatjana Wedig, Nathalie Schwarz, Florian Iser, Jochen Meyer, Felix Sahm, Benedikt Brors, Hannu Haapasalo, Stefan M Pfister, Joonas Haapasalo, Kristian W Pajtler, Kristiina Nordfors
Journal: Neuro-Oncology (2022)

Abstract BACKGROUND: Liquid biopsies (LBs) hold great promise as a non-invasive method for tumor detection and disease monitoring. Their application in pediatric neuro-oncology patients has been challenging due to the blood-brain barrier limiting the amount of circulating tumor DNA (ctDNA) and low volumes of cerebrospinal fluid (CSF) and serum samples. Here, we assessed the feasibility of LBs in a pediatric brain tumor cohort (n=12 patients) by adapting pre-analytical protocols to low cell-free DNA (cfDNA) input and bioinformatic pipelines for genome-wide analyses. METHODS: Genomic DNA isolated from tumor tissues, including medulloblastoma (n=6), ependymoma (n=4), low-grade glioma (n=1), and choroid plexus papilloma (n=1), and cfDNA isolated from matched CSF and serum samples were subjected to low-coverage whole genome sequencing (lcWGS) and the EPIC DNA methylation array. For methylation analyses, samples were prepared using both traditional bisulfite- and recently developed enzymatic-based methylation conversion. Molecular tumor (sub)type predictions were performed using the Heidelberg Brain Tumor Classifier. RESULTS: lcWGS revealed tumor-specific copy number variations (CNVs) in both CSF and serum samples. The detection rate of tumor-specific CNVs (median 92% vs. 23%) and the ctDNA fraction (median 31% vs. 1.5%) were higher in CSF vs. serum samples. Bisulfite-converted as well as enzymatically converted tumor DNA and cfDNA samples could be readily analyzed using the Heidelberg Classifier. In comparison to bisulfite-based conversion, enzymatic-based conversion improved the quality of methylation analyses for minimal input cfDNA samples. CONCLUSIONS: Our results highlight the feasibility of liquid biopsies from both CSF and serum in brain tumor patients. In contrast to CNV-based tumor detection from serum samples, ctDNA analysis from CSF allowed a more comprehensive genetic and epigenetic profiling which is expected to assist in less-invasive tumor classification, identification of drug targets, or the investigation of tumor evolution. Altogether, this study provides the rationale for further implementation of LBs in pediatric neuro-oncology.
The role of ACAA2 in colorectal caner patient with active glucose metabolism.
Authors: Yitao Yuan, Tianshu Liu, Mengling Liu, Lu Gan
Journal: Journal of Clinical Oncology (2022)

e15522 Background: colorectal cancer(CRC) is third in incidence and mortality in worldwide with a 5-year survival rate is 65%. CRC patients(pts) with active glucose metabolism have a worse outcome. Molecular biological mechanisms in this subgroup have not been well uncovered. Here we identified ACAA2 has a significant prognostic role in CRC pts and more down-regulated in those with higher standardized uptake value(SUV). Then we focused on its functions and mechanisms behind it. Methods: Clinical and transcriptional data of pts with CRC obtained from GSE39582 dataset (n = 510) and a Zhongsh an Hospital Fudan University Cohort(ZHFUC) with CRC diagnosed at 6/2015-12/2018 were collected (n = 441). The ACAA2 protein expression of ZHFUC was evaluated by immunohistochemistry staining. Metabolic activity was evaluated by SUV. Overall survival (OS) was analyzed via Kaplan-Meier Curves with Log-rank test and multivariable Cox regression. Silencing (KD) and over-expression (OE) of ACAA2 were performed in CRC cells, respectively(KD: HCT116;RKO and OE: DLD1;RKO). The effect of ACAA2 was tested through CCK8, colony formation assays, cell cycle assays, seahorse for glucose metabolism and subcutaneous xenograft models. The potential mechanism under ACAA2 contribution was explored by RNA sequencing and western blot. Results: ACAA2 of ZHFUC was down-regulated in CRC compared to normal tissues. Pts divided into ACAA2 high (n = 226) and low (n = 215) with an evenly distribution in their clinicopathological features.Of 143 pts with available PETCT imaging took as a SUV-related group), 78 were identified as ACAA2 high and 65 were low. In comparison to ACAA2 high ones, pts in ACAA2 low showed an higher SUV (p &lt; 0.05) and a significantly worse OS (total pts: p = 0.012; SUV-related group:p = 0.024; median OS is not reached). The multivariate analysis showed that ACAA2 low was independently associated with inferior OS [total pts: HR 1.99(95%CI: 1.2 ¨C 3.2), p &lt; 0.001; SUV-related group: HR 2.51(95%CI: 1.1 ¨C 5.7), p =&lt; 0.05]. Over-expression ACAA2 inhibited tumor growth both in vitro and in vivo, and lower glucose metabolism and arrested G0/G1 cell cycle were observed in HCT116-OE cells, while reversed effects in RKO-KD cells. gene expression profiling analysis and consistent results in western blot highlighted the role of AKT signaling pathway in those contributions of ACAA2. A AKT inhibitor could suppress cell proliferation causing by silencing ACAA2 both in vitro and in vivo. Conclusions: while ACAA2 expression was an independent prognostic factor for CRC pts. And those of them with an active glucose metabolism had a lower ACAA2 expression. The silencing and over-expression of ACAA2 expression in CRC cell lines promoted and inhibited cell proliferation and tumor growth in vitro and in vivo, oppositely. ACAA2 expression levels might classified a subtype of CRC pts, who might benefit from AKT inhibitors treatment.
Collagen bundle orientation by Fourier analysis in myocardial infarction scarring
Authors: V Marcos Garces, C Rios-Navarro, F Gomez-Torres, J Gavara, E De Dios, N Perez, A Diaz, G Minana, FJ Chorro, V Bodi, A Ruiz-Sauri
Journal: Cardiovascular Research (2022)

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): “Instituto de Salud Carlos III” and “Fondos Europeos de Desarrollo Regional FEDER” and Conselleria de Educación – Generalitat Valenciana. Introduction After acute myocardial infarction (AMI), the lack of oxygen and nutrients leads to cardiomyocyte necrosis and eventually to the formation of a collagen-based scar. Infarct scar characteristics, such as collagen bundle orientation, have a relevant influence on scar mechanics, the occurrence of cardiac arrhythmias, left ventricular dilation or aneurysm formation, wall stiffness, and the development of wall rupture or heart failure. However, the most adequate method for collagen bundle orientation (CBO) measurement in myocardial scar is not established. Purpose We aim to compare the measurement of collagen bundle orientation in infarct scar by Fourier analysis in three different histopathological techniques. Methods Juvenile swine (n=21) were subjected, by means of percutaneous balloon inflation, to a transient 90-min occlusion of mid left anterior descending artery followed by one month of reperfusion (chronic AMI group). Samples were obtained from the infarcted zone and stained with Masson’s trichrome, Picrosirius red and Haematoxylin-Eosin (H-E) standard protocols. Five microphotographs of the myocardial scar were taken at 200x magnification with light, polarised and confocal microscopy, respectively. A single observer measured CBO by means of Fast Fourier Transform analysis using a semi-automated protocol. Comparability between techniques was studied by the Intraclass Correlation Coefficient (ICC), the coefficient of variation (CV) and the Bland-Altman (B&amp;A) plots and limits of agreement. Results Measurement of CBO in Masson’s trichrome tended to show higher (more "random-oriented") values than in Picrosirius and H-E+confocal techniques (ICC 0.79 and 0.7, p=0.001 and 0.005; B&amp;A 0.29 to -0.02 and 0.43 to 0.01; CV 6.97% and 12.98%, respectively). However, measurement of CBO in Picrosirius and H-E+confocal techniques showed an "almost perfect" agreement (ICC 0.84, p&amp;lt;0.001; B&amp;A 0.28 to -0.09; CV 17.33%). Selective staining and/or visualization of collagen in these latter techniques may underlie our findings, contrary to non-selective Masson’s trichrome. Conclusion Picrosirius red staining (visualized with polarised microscopy) and Haematoxylin-Eosin (visualized with confocal microscopy) are comparable in terms of collagen bundle orientation measurement by Fourier analysis in an animal model of chronic infarct scar. Masson’s trichrome (visualized with light microscopy) tends to show more "random-oriented" values, potentially due to non-specific staining and visualization of non-collagenous structures such as cells, and should not be recommended for this specific purpose.
Oxidative stress causes nocturnal polyuria via the SPAK-NCC pathway in the kidney: Amelioration by a novel antioxidant, silicon component agents
Authors: Y. Sekii, H. Kiuchi, T. Imanaka, S. Kuribayashi, K. Okada, K. Takezawa, S. Fukuhara, N. Nonomura
Journal: European Urology (2022)
Chemokines and chemokine receptors in colorectal cancer; multifarious roles and clinical impact
Authors: Maria Braoudaki, Mohammed Saqif Ahmad, Denis Mustafov, Sara Seriah, Mohammad Naseem Siddiqui, Shoib Sarwar Siddiqui
Journal: Seminars in Cancer Biology (2022)

Colorectal cancer (CRC) is considered the second cause of cancer death worldwide. The early diagnosis plays a key role in patient prognosis and subsequently overall survival. Similar to several types of cancer, colorectal cancer is also characterised by drug resistance and heterogeneity that contribute to its complexity -especially at advanced stages. However, despite the extensive research related to the identification of biomarkers associated to early diagnosis, accurate prognosis and the management of CRC patients, little progress has been made thus far. Therefore, the mortality rates, especially at advanced stages, remain high. A large family of chemoattractant cytokines called chemokines are known for their significant role in inflammation and immunity. Chemokines released by the different tumorous cells play a key role in increasing the complexity of the tumour's microenvironment. The current review investigates the role of chemokines and chemokine receptors in colorectal cancer and their potential as clinical molecular signatures that could be effectively used as a personalised therapeutic approach. We discussed how chemokine and chemokine receptors regulate the microenvironment and lead to heterogeneity in CRC. An important aspect of chemokines is their role in drug resistance which has been extensively discussed. This review also provides an overview of the current advances in the search for chemokines and chemokine receptors in CRC.
Evaluation of the utility of lymph-vascular invasion as an independent prognostic predictor of overall survival for patients with renal cell carcinoma that undergo nephrectomy
Authors: I. Ivan, N. Rakic, N. Corsi, A. Piontkowski, S. Majdalany, M. Jamil, A. Sood, D. Dalela, S. Arora, C. Rogers, F. Abdollah
Journal: European Urology (2022)
Lipopolysaccharide from gut microbiota promotes prostate cancer growth through histamine H1 receptor signaling
Authors: K. Fujita, M. Matsushita, D. Motooka, H. Hase, E. Banno, M.A. De Velasco, T. Kato, K. Hatano, A. Kawashima, M. Uemura, S. Nakamura, K. Tsujikawa, E. Morii, H. Uemura, N. Nonomura
Journal: European Urology (2022)
A Rare Extramedullary Involvement Site in Patients With Multiple Myeloma
Authors: Seda Gülbahar Ateş, Gülin Uçmak
Journal: Clinical Nuclear Medicine (2022)

Multiple myeloma (MM) is a hematologic malignancy associated with uncontrolled clonal proliferation of plasma cells. Extramedullary disease in MM is an aggressive entity with a poor prognosis. Moreover, involvement of the gastrointestinal tract is a rare aggressive biological sign. 18 F-FDG PET/CT is an irreplaceable modality in the assessment of extramedullary disease. We present 2 cases with gastric involvement of MM that were shown by 18 F-FDG PET/CT and confirmed as plasma cell infiltration pathologically. 18 F-FDG PET/CT studies of MM patients should be interpreted carefully for gastrointestinal involvement, and it should be kept in mind that it can mimic other malignancies.
Highlights From the <i>Circulation</i> Family of Journals
Authors: Alex Christensen, ; Christoffer, Rasmus Vissing, Adrian Pietersen, Jacob Tfelt-Hansen, Thomas Hartvig, Lindkaer Jensen, Steen Pehrson, ; Finn, Lund Henriksen, Niels Christian, Foldager Sandgaard, ; Kasper, Karmark Iversen, Henrik Kjaerulf Jensen, ; Morten, Salling Olesen, Henning Bundgaard, Elisabeth Widén, Nella Junna, Sanni Ruotsalainen, Ida Surakka, Nina Mars, Pietari Ripatti, Juulia Partanen, Johanna Aro, Pekka Mustonen, Tiinamaija Tuomi, Aarno Palotie, Veikko Salomaa, Jaakko Kaprio, Jukka Partanen, Kristina Hotakainen, Pasi Pöllänen, Samuli Ripatti, Gaurav Gulati, Jenica Upshaw, Benjamin Wessler, Riley Brazil, Jason Nelson, David Van Klaveren, Christine Lundquist, Jinny Park, Hannah Mcginnes, Ewout Steyerberg, Ben Van Calster, David Kent, Kady Fischer, Dominik Guensch, Bernd Jung, Iman King, Hendrik Von Tengg-Kobligk, Nadia Giannetti, Balthasar Eberle, Matthias Friedrich, Krishna Patel, Poghni Peri-Okonny, Raed Qarajeh, Femina Patel, Brett Sperry, ; Mcghie, Randall Thompson, Kevin Kennedy, Paul Chan, John Spertus, Timothy Bateman
Journal: Circulation (2022)

A novel inherited cause of polymorphic ventricular tachycardia called Familial ST-Depression Syndrome is described in Circulation: Arrhythmia and Electrophysiology.In Circulation: Genomic and Precision Medicine, the effect of reporting polygenic risk scores on health behaviors is described.A large-scale evaluation of clinical risk prediction models is described in Circulation: Cardiovascular Quality and Outcomes.The impact of myocardial oxygenation reserve on heart failure with preserved ejection fraction is presented in Circulation: Heart Failure.The independent association of reduced myocardial flow reserve with mortality is described in Circulation: Cardiovascular Imaging.Last, outcomes of moderate left main disease from the ISCHEMIA trial (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches) are presented in Circulation: Cardiovascular Interventions.
Radical cystectomy for bladder cancer in patients previously treated for prostate cancer: Perioperative and oncological outcomes
Authors: S. Tappero, S. Parodi, G. Mantica, M. Borghesi, C. Fiori, M. Manfredi, M. Bandini, A. Mari, F. Valastro, M.A. Cerruto, A. Gozzo, F. Chessa, R. Schiavina, A. Briganti, A. Minervini, A. Antonelli, F. Porpiglia, E. Brunocilla, F. Montorsi, N.R. Suardi, C. Terrone
Journal: European Urology (2022)
RONC-11. Permanent alopecia in pediatric patients with medulloblastoma treated by craniospinal irradiation: looking for a threshold dose
Authors: Camilla Satragno, Antonio Verrico, Flavio Giannelli, Alfonso Ferrero, Francesca Cavagnetto, Irene Schiavetti, Maria Luisa Garrè, Federica Garibotto, Claudia Milanaccio, Antonia Ramaglia, Sonia Di Profio, Liliana Belgioia, Salvina Barra
Journal: Neuro-Oncology (2022)

Abstract BACKGROUND: Permanent alopecia in adult survivors of childhood cancer is a late effect that has a negative impact on vitality and social function, and it is not clear if it is only associated with radiotherapy or also with high-dose chemotherapy. In this study, we analysed a cohort of medulloblastoma survivors treated with craniospinal irradiation (CSI) with long follow-up looking for radiotherapy parameters associated with permanent hair loss. METHODS: We retrospectively analysed 42 patients with medulloblastoma with median follow up of 10 years. In 27 pts, Eclipse subgroup, the scalp was accurately re-contoured and were estimated specifics dosimetric parameters. Any relationship between presence of alopecia and other characteristics was investigated by univariate and multivariate analysis, in both groups. For each significant predictor variable, a Receiver Operating Characteristic curve was drawn for calculating the Area Under the Curve and identifying the optimal dose discriminatory cut-off value for prediction of alopecia. RESULTS: The best predictor for the occurrence of permanent alopecia was the dose of CSI (OR: 1.002; 95%CI: 1.001-1.003; p=0.003), with a cut-off value of 30.9 Gy. In Eclipse subgroup median Dose hair skin was statistically significant, (OR: 1.216; 95%CI: 1.030-1.435; p=0.021), with a cut-off value of 28.7 Gy. If the median dose of each Gy unit of D median is exceeded, the probability of alopecia increases by 21.6% (3.0% - 43.5%), with a specificity of 90.9%. None of the other variables was statistically significant. CONCLUSIONS: Pediatric Medulloblastoma survivors have a high risk of developing permanent alopecia.Our study supports the finding that permanent hair loss is dose-dependent and identified a threshold dose, the median dose of 28.7 Gy, to prevent the occurrence of permanent alopecia in paediatric patients undergoing radiotherapy. Therefore, we suggest that this dosimetric parameter should be evaluated when planning radiation treatment, especially when planning CSI in low- and standard-risk medulloblastoma.
ETMR-13. Embryonal Tumor with Multilayered Rosettes in an Infant: Case Report
Authors: Llarx Saundt Yu, Eric Paolo Palabyab, Ronnie Baticulon
Journal: Neuro-Oncology (2022)

Abstract Embryonal tumor with multilayered rosettes (ETMR) is a highly malignant tumor (WHO grade 4) seen predominantly in infants. It includes morphologically distinct embryonal tumors namely, embryonal tumor with abundant neuropil and true rosettes, ependymoblastoma, and medulloepithelioma. The presence of multilayered rosettes and C19MC amplification at chromosome 19q13.42 confirms the diagnosis. The median overall survival is less than a year and the prognosis is generally poor. We report the case of a 1-year-old girl who presented with vomiting, lethargy, and increasing head circumference over a period of six months. On admission, she was drowsy and irritable. Verbal output was limited to moans and motor response was localizing. She was macrocephalic with a head circumference of 51 cm. MRI showed a large 5 x 5 x 6.5cm contrast-enhancing cerebellar vermian tumor with obstructive hydrocephalus. There was no evidence of leptomeningeal disease or spinal metastasis at this time. She underwent a right frontal ventriculoperitoneal shunt insertion, followed by suboccipital craniotomy and subtotal tumor resection one week later. Her shunt was ligated two days after tumor excision, due to development of bilateral subdural hygromas. The patient regained full consciousness, but still had spastic lower extremities and inability to swallow at the time of discharge. Histopathology and immunostains were consistent with an embryonal tumor, possibly ETMR, and the patient was for advised chemotherapy. Before initation of chemotherapy, the patient was admitted in another instution because of alteration in sensorium. Repeat imaging showed progression of the patient’s subdural hygromas, requiring insertion of a subduroperitoneal shunt. The patient died seven weeks after tumor resection due to progression of her tumor residual. Management options for ETMR are limited, especially in low- and middle-income countries. International linkages may help facilitate the accurate diagnosis and early treatment of these patients with rare but aggressive brain tumors.
Topographic description of the site of positive MpMRI and impact on the risk of positive surgical margins at robot-assisted nerve sparing radical prostatectomy: Implications for accurate surgical approaches
Authors: F.M. Barletta, S. Scuderi, G. Rosiello, A. Stabile, G. Gandaglia, E. Mazzone, A. Gallina, N. Fossati, E. Zaffuto, F. Dehò, U. Capitanio, V. Mirone, A. Larcher, A. Salonia, P.I. Karakiewicz, S. Shariat, F. Montorsi, A. Briganti
Journal: European Urology (2022)
Overall Survival Update for Patients with Metastatic Castration-resistant Prostate Cancer Treated with Capivasertib and Docetaxel in the Phase 2 ProCAID Clinical Trial
Authors: Simon J. Crabb, Gareth Griffiths, Denise Dunkley, Nichola Downs, Mary Ellis, Mike Radford, Michelle Light, Josh Northey, Amy Whitehead, Sam Wilding, Alison J. Birtle, Vincent Khoo, Robert J. Jones
Journal: European Urology (2022)

The PI3K/AKT/PTEN pathway is frequently deregulated in metastatic castration-resistant prostate cancer (mCRPC). ProCAID was a phase 2 trial assessing addition of the AKT1/2/3 inhibitor capivasertib to docetaxel for patients with mCRPC. We previously reported that capivasertib did not extend a composite progression-free survival primary endpoint but did significantly improve the secondary endpoint of overall survival (OS). Here we present OS data after 66% of events had occurred in the intent-to-treat population (n = 150). Median OS was 25.3 mo for capivasertib plus docetaxel versus 20.3 mo for placebo plus docetaxel (hazard ratio [HR] 0.70, 95% confidence interval [CI] 0.47-1.05; nominal p = 0.09). Receipt of subsequent life-extending treatments was balanced between the treatment arms. The OS benefit associated with capivasertib was maintained in a subset of patients previously treated with abiraterone and/or enzalutamide (median OS 25.0 vs 17.6 mo; HR 0.57, 95% CI 0.36-0.91; nominal p = 0.02) but not in abiraterone/enzalutamide-naïve patients (median OS 31.1 mo vs not reached; HR 1.43, 95% CI 0.63-3.23). We conclude that OS may be extended by addition of capivasertib to docetaxel. Exploratory analysis revealed that the OS benefit was maintained in a subset of patients previously exposed to androgen receptor-targeted agents, which should be evaluated in prospective trials. PATIENT SUMMARY: The ProCAID study examined whether adding the AKT inhibitor drug capivasertib to docetaxel chemotherapy improves outcomes for patients with advanced prostate cancer. Initial analysis of the ProCAID results suggested that capivasertib improved overall survival benefit. This follow-up analysis suggests that capivasertib addition may be particularly beneficial for patients whose cancer was previously treated with drugs that target the androgen receptor.